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. 2019 Feb 25;58(9):2685-2691.
doi: 10.1002/anie.201812535. Epub 2019 Feb 6.

Racemic Vinylallenes in Catalytic Enantioselective Multicomponent Processes: Rapid Generation of Complexity through 1,6-Conjugate Additions

Youming Huang  1 , Sebastian Torker  1 , Xinghan Li  1 , Juan Del Pozo  1 , Amir H Hoveyda  1
Affiliations

Racemic Vinylallenes in Catalytic Enantioselective Multicomponent Processes: Rapid Generation of Complexity through 1,6-Conjugate Additions

Youming Huang et al. Angew Chem Int Ed Engl. .

Abstract

Racemic vinylallenes are shown to be effective substrates for catalytic multicomponent diastereo- and enantioselective 1,6-conjugate addition of multifunctional allyl moieties to easily accessible α,β,γ,δ-unsaturated diesters. Reactions may be catalyzed by 5.0 mol % of a readily accessible NHC-Cu complex at ambient temperature, and other than a vinylallene, involve B2 (pin)2 and an α,β,γ,δ-unsaturated diester. A variety of vinylallenes were converted to products bearing a Z-trisubstituted alkenyl-B(pin) moiety, a vinyl group, a β,γ-unsaturated diester unit, and vicinal stereogenic centers in up to 67 % yield, 87:13 Z/E ratio, >98:2 d.r., and 98:2 e.r. Chemoselective modifications involving the alkenyl-B(pin), the vinyl, or the 1,2-disubstituted olefin moieties were carried out to demonstrate versatility and utility. Stereochemical models, based on mechanistic and DFT studies, demonstrate the dynamic behavior of intermediated Cu-allyl species and account for various selectivity profiles.

Keywords: 1,6-conjugate additions; boron; copper; enantioselective catalysis; vinylallenes.

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Figures

Scheme 1.
Scheme 1.
General strategy pursued in this study. G, R, carbon-based substituents; pin, pinacolato; L, ligand.
Scheme 2.
Scheme 2.
Identification of an effective NHC–Cu complex. [a] Conv. (±2%; loss of 1a), Z:E ratio, and d.r. (±2%) determined by analysis of 1H NMR spectra of unpurified mixtures. [b] Yield (±5%, average of at least three runs) is for purified product (Z/E mixture). [c] E.r. determined by HPLC analysis. See the Supporting Information for details.
Scheme 3.
Scheme 3.
Transformations with different alkyl-substituted dienoates and vinylallenes. See the Supporting Information for details.
Scheme 4.
Scheme 4.
Exploration of the utility of the catalytic multicomponent method. See the Supporting Information for details. dbu, 1,8-diazabicyclo[5.4.0]undec-7-ene;TBS, t-butyldimethyl silyl; MOM, methoxymethyl.
Scheme 5.
Scheme 5.
Studies regarding pathways that cause lower Z:E selectivity. Abbreviations: ts = transition state.
Scheme 6.
Scheme 6.
Stereochemical models accounting for the various stereoselectivity issues.
See this image and copyright information in PMC

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